Synthesis of benzocyclobutenes by palladium-catalyzed C-H activation of methyl groups: method and mechanistic study.
An efficient catalytic system has been developed for the synthesis of benzocyclobutenes by C-H activation of methyl groups. The optimal conditions employed a combination of Pd(OAc) 2 and P ( t )Bu 3 as catalyst, K 2CO 3 as the base, and DMF as solvent. A variety of substituted BCB were obtained under these conditions with yields in the 44-92% range, including molecules that are hardly accessible by other methods. The reaction was found limited to substrates bearing a quaternary benzylic carbon, but benzocyclobutenes bearing a tertiary benzylic carbon could be obtained indirectly from diesters by decarboxylation. Reaction substrates bearing a small substituent para to bromine gave an unexpected regioisomer that likely arose from a 1,4-palladium migration process. The formation of this "abnormal" regioisomer could be suppressed by introducing a larger subsituent para to bromine. DFT(B3PW91) calculations on the reaction of 2-bromo-tert-butylbenzene with Pd(P ( t )Bu 3) with different bases (acetate, bicarbonate, carbonate) showed the critical influence of the coordination mode of the base to induce both an easy C-H activation and to allow for a pathway for 1,4-palladium migration. Carbonate is shown to be more efficient than the two other bases because it can abstract the proton easily and at the same time maintain kappa (1)-coordination without extensive electronic reorganization.
Chaumontet
Manon
M
Institut Charles Gerhardt, UMR5253, CNRS-UM2-UM1-ENSCM, case courrier 1501, Place Eugène Bataillon, 34000 Montpellier, France.
Piccardi
Riccardo
R
Audic
Nicolas
N
Hitce
Julien
J
Peglion
Jean-Louis
JL
Clot
Eric
E
Baudoin
Olivier
O
D002384:Catalysis; D010165:Palladium / Q000737:chemistry; D011083:Polycyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry
D011083:Polycyclic Compounds; C079040:benzocyclobutene; D010165:Palladium